The purpose of the present study is to address the relationship between physical activity history and brain processes in older men and women (50 - 65 years), particularly in those who are genetically at risk for late-onset Alzheimer's Disease (i.e., carriers of the APOE e4 allele. Neuroimaging studies reveal relative hypoactivation of brain metabolism in cognitively normal middle-aged e4 carriers during mental challenge in hippocampus and prefrontal cortex, indicative of metabolic abnormality in the same brain regions that are involved in AD. Recent epidemiological study indicates that physically active older e4 carriers show remarkable attenuation in cognitive decline relative to sedentary carriers of e4. In addition, recent animal research indicates neurotrophic effects of voluntary exercise on the hippocampal region. Collectively, these studies suggest an ameliorative influence of physical activity on the aging brain and a potential slowing of early-stage AD progression. Accordingly, 52 participants classified by physical activity level (high v low) and genotype (e4 allele present v absent) to form four groups will undergo magnetic source imaging (MEG) to assess hippocampal and prefrontal activity during cognitive challenge. We predict that physical activity status in middle-aged men and women will be associated with higher activity in hippocampus and lower activity in prefrontal region. Furthermore, the magnitude of these differences will be greatest between active and low-active carriers of the e4 allele. Detection of such related differences in brain activity in middle-aged adults would suggest an ameliorative influence of physical activity on age-related neurodegeneration and a protective role for AD progression. [unreadable] [unreadable] [unreadable] [unreadable]